P53 activation promotes MCL1 degradation through downregulating the RAS/RAF/MEK/ERK signaling pathway, therefore, MDM2 inhibitor in combination with BCL2 inhibitor overcomes MCL1-mediated apoptotic resistance and shows synergistic lethality of relapsed/refractory AML in preclinical and clinical trials (115) (Table 1). The gene discussed is MCL1; the disease is acute myeloid leukemia.